Novel non-reverting salmonella live vaccines

Drug – bio-affecting and body treating compositions – Whole live micro-organism – cell – or virus containing – Genetically modified micro-organism – cell – or virus

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424 87, 4351721, 4351723, 435245, 435253, 435879, 935 1, 935 9, 935 31, 935 58, 935 65, 935 72, A61K 3902, C12N 1500, C12N 136, C12N 120

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047358017

ABSTRACT:
Live vaccines are provided and methods for preparing the live vaccines for protection of a host from a pathogenic microorganism. The vaccines are prepared by introducing at least one modification in a gene involved in at least one, normally at least two, biosynthetic pathways, involving the production of products which are unlikely to be found in the disease susceptible host. The modification results in a gene change which cannot be repaired by a single step e.g. polynucleotide deletions and inversions. Where the aro gene suffers such a change, the resultant auxotrophic mutants require aromatic amino acids, p-aminobenzoic acid and 2,3-dihydroxybenzoic acid or a highly concentrated source of absorbable iron. The auxotrophic mutations have substantially reduced or nonexistent virulence, while retaining the desired immunogenicity to initiate the immunogenic response. Various techniques can be employed for providing the desired change.
Salmonella typhimurium strain SL1479 was deposited at the ATCC on Sept. 7, 1982 and given ATCC Accession No. 39183; Salmonella dublin strain SL1438 was deposited on Sept. 7, 1982 at the ATCC and given ATCC Accession No. 39184.
Salmonella typhi strain 531Ty was deposited at the ATCC on Nov. 21, 1984, and granted ATCC Accession No. 39926.

REFERENCES:
patent: 4337314 (1982-06-01), Oeschger et al.
Yancey, Infection and Immunity, vol. 24, 174 (1979).
Morris et al., Brit. J. Exp. Path, vol. 57: 354 (1976).
Kleckner et al., J. Mol. Biol., vol. 116, 125 (1977).
Kleckner et al., J. Mol. Biol., vol. 127, 89 (1977).
Kleckner et al., Genetics, vol. 90: 427-464 (1978).
Brock et al., Biology of Microorganisms, 1970, pp. 304-307, Prentice-Hall, N.J.

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